In addition to the role oral infections play in promoting tooth loss, periodontitis has also been associated with increasing the risk of other medical conditions such as coronary artery disease, stroke and myocardial infarction. Approximately 50% of the US population over 20 years of age has gingivitis around 3 or more teeth, and 5% have advanced periodontitis. Due to the prevalence of periodontal infections, even a marginal decrease in the risk of periodontitis could affect the occurrence of these other conditions for millions of Americans. The current standard of care for periodontitis is mechanical debridement (scaling and root planing). Adjunctive antibiotic therapies have been tested for the prevention of subsequent bacterial recolonization with mixed effectiveness. Systemic antibiotics, as well as local irrigation with antibiotic solutions have demonstrated some improvement in prolonging the effects of debridement. However, recent advances in biomaterials and drug-eluting polymers have given rise to a number of strategies for the controlled release and localized retention of antibiotic to at-risk subgingival sites. While these approaches have improved periodontitis treatment, none have attempted to target the affected tissue directly, instead relying on the biomaterial or polymer to regulate drug release and retention. Affinergy Inc. is developing site-specific targeting peptides, we have termed interfacial biomaterials (IFBMs) designed to bind a therapeutic agent and a target substrate (medical implant or tissue). Using phage display technology, peptide sequences can be targeted to a material, molecule or tissue type using a randomized phage library, capable of testing billions of candidate sequences in one experiment. By pairing a material-binding peptide with a therapeutic-binding peptide, we generate a novel bifunctional peptide, capable of directing biological activity on an implanted surface. In the current proposal, we aim to target antibiotics directly to teeth and gingiva using high-affinity peptides fostering the retention and sustained release of antibiotics in regions susceptible to periodontal infection. Our previous work has identified high-affinity peptides that bind the glycopeptide antibiotic vancomycin, which we hope to build upon by targeting the gram- negative-killing drug minocycline. Linking these peptides, with teeth and gingiva-binding peptides will give rise to a novel peptide-based antibiotic delivery molecule. PUBLIC HEALTH RELEVANCE: Oral infections are one of the most common infections in the US, with 50% of Americans over 20 years of age affected by gingivitis, and 5% with advanced periodontitis. Therefore, approximately 15 million people require a cost-effective antibiotic delivery system to treat this infection. Here we propose the development of a high-affinity peptide-based platform for the delivery of minocycline to teeth and gingiva. Affinergy has identified dozens of target-specific peptides for a wide range of molecules, tissues and materials using phage display technology. Generating peptide sequences which bind minocycline, teeth and gingiva, will provide the component peptides to synthesize a bifunctional peptide linker to attach antibiotics to these tissue surfaces. The final goal of this proposal is to generate a peptide prototype, capable of long-term retention of minocycline to teeth and gums toward the treatment and prevention of periodontitis.